Charcot-Marie-Tooth disease (CMT) is the most common inherited peripheral neuropathy, causing progressive weakness and sensory loss that typically begins in the feet and legs and later affects the hands. It is caused by mutations in dozens of different genes involved in myelin production or axonal function. There is currently no disease-modifying treatment, though many people live active lives with supportive care.
What's actually going on in research
The most common form, CMT1A — caused by a duplication of the PMP22 gene — has attracted the most drug development activity, with antisense oligonucleotides (ASOs) and gene-silencing approaches aiming to reduce excess PMP22 protein. Separate programs address CMT1B (MFN2-related) and X-linked CMT. Gene therapy using AAV vectors is in early-phase trials for several subtypes, and small molecules targeting the unfolded protein response and neuroinflammation are also in development.
PMP22-targeting gene silencing
ASOs and RNA interference approaches designed to reduce overexpression of PMP22 in CMT1A are in early clinical trials, representing the first potential disease-modifying treatments for this common subtype.
AAV gene therapy
For rarer CMT subtypes with loss-of-function mutations, AAV-based gene replacement therapy is in early-phase trials, with programs for CMT1B, CMT4C, and X-linked forms advancing.
Neuroprotection and regeneration
Small molecules aimed at reducing endoplasmic reticulum stress, neuroinflammation, and axonal degeneration are being studied as broadly applicable approaches across multiple CMT genetic subtypes.
What to know before you search
Eligibility usually requires genetically confirmed CMT subtype, documented nerve conduction abnormalities, and absence of other neuropathy causes.
What types of trials are currently open
- Gene silencing trials — Testing ASO and RNAi therapies targeting PMP22 overexpression in CMT1A patients.
- Gene therapy trials — AAV-based gene replacement for loss-of-function CMT subtypes including CMT1B and X-linked CMT.
- Small molecule trials — Evaluating drugs that reduce unfolded protein response and axonal stress across CMT subtypes.
- Rehabilitation and biomarker studies — Identifying functional outcome measures and MRI-based biomarkers to track disease progression.
- Natural history studies — Characterizing disease progression in genetically confirmed CMT to enable future trial design.
Recently added Charcot-marie-tooth Disease trials
TREMOR IN CHARCOT-MARIE-TOOTH
Tremor is a symptom that has already been described in many case reports and case series concerning patients with Charcot-Marie-Tooth (CMT) disease. However, the pathophysiology of tremor in this condition remains largely unclear. It has also not been sufficiently investigated to what extent tremor in CMT patients constitutes a relevant impairment of quality of life. This project focuses on a more detailed characterization of tremor in CMT patients using surface electromyography and accelerometer analysis, as well as the collection of individual clinical data, particularly regarding the symptom of tremor, in order to facilitate the characterization and etiological classification of the tremor. In addition, a questionnaire-based assessment will be conducted to capture the impact of tremor on activities of daily living and the associated burden in this specific patient cohort. The entire data collection process will be supported by a clinical examination, which will be video-recorded by experienced neurologists to ensure more reliable analysis. This serves both the characterization of tremor and the illustration of its functional limitations. Where available, the data will be correlated with genetic variants to allow conclusions about possible genetic predispositions or disease progression. As a control group, CMT patients who have not yet reported a tremor will be included.
AUTONOMOUS DISORDERS IN CMT
Hereditary neuropathies are a phenotypically and genetically heterogeneous group of disorders. One of the most common forms is Charcot-Marie-Tooth neuropathy (CMT), which can be further divided into demyelinating (CMT1) and axonal (CMT2) neuropathies, as well as various pathogenic genetic variants. In addition to the clinically predominant motor and sensory deficits, symptoms of the autonomic nervous system have also been described in patients with CMT, often leading to significant limitations in daily functioning and quality of life. However, little is known about the prevalence and extent of autonomic dysfunction in CMT patients. In this study, patients with CMT will be assessed for the presence, severity, and characteristics of autonomic dysfunction using questionnaires and non-invasive diagnostic methods. Furthermore, diagnosis, genotype, and individual disease data-such as disease duration, severity of neurological impairment, and comorbidities-will be collected from patient records. The aim of this study is to evaluate and characterize autonomic dysfunction in patients with CMT. It seeks to determine how frequently autonomic dysfunction occurs in CMT, which areas of the autonomic nervous system are most commonly affected, whether risk factors exist, and what differences can be observed between the various CMT subtypes. The findings of this study are expected to provide new insights into the role of autonomic dysfunction in CMT, ultimately contributing to improved care and treatment for affected patients.
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